Thomas Arendt - Selected Publications#
Web of Science: H-index 72.
1. Nitsche A, Arnold C, Ueberham U, Reiche K, Fallmann J, Hackermüller J, Horn F, Stadler PF, Arendt T. Alzheimer-related genes show accelerated evolution. Mol Psychiatry. 2021; 26(10) 5790-5796.
This paper shows that the gene-structures of loci, that exhibit AD-associated changes in their expression, evolve faster than the genome at large. The accelerated evolution of AD-associated-genes indicates a more rapid functional adaptation of these genes. In particular AD-associated non-coding-genes play an important, as yet largely unexplored, role in AD. This phylogenetic trait indicates that recent adaptive evolution of human brain is causally involved in basic principles of neurodegeneration. It highlights the necessity for a paradigmatic change of our disease-concepts and to reconsider the appropriateness of current animal-models to develop disease-modifying strategies that can be translated to human.
2. Doehner W, Praße L, Wolpers J, Brückner MK, Ueberham U, Arendt T. Transgenerational transmission of an anticholinergic endophenotype with memory dysfunction. Neurobiol Aging. 2017; 51:19-30.
This paper suggest an epigenetic trait for an anticholinergic endophenotype associated with cognitive dysfunction which might be relevant to our understanding of mental impairment in neurodegenerative disorders such as Alzheimer's disease and related disorders.
3. Arendt T, Brückner MK, Lösche A. Regional mosaic genomic heterogeneity in the elderly and in Alzheimer's disease as a correlate of neuronal vulnerability. Acta Neuropathol. 2015;130(4):501-10
This paper shows that neurons with a more-than-diploid content of DNA are increased in preclinical stages of Alzheimer’s disease (AD) and are selectively affected by cell death during progression of the disease. Hyperploidy of neurons thus represents a direct molecular signature of cells prone to death in AD and indicates that a failure of neuronal differentiation is a critical pathogenetic event in AD.
4. Arendt T, Bullmann T. Neuronal plasticity in hibernation and the proposed role of the microtubule-associated protein tau as a "master switch" regulating synaptic gain in neuronal networks. Am.J.Physiol.Regul.Integr.Comp.Physiol. 2013; 305 (5):R478-89.
This paper puts forward the concept of the microtubule-associated protein tau as a kind of "master switch," regulating NMDA receptor-mediated synaptic gain in a wide array of neuronal networks, under conditions of reduced metabolism during the entry into torpor.
5. Fischer HG, Morawski M, Brückner MK, Mittag A, Tarnok A, Arendt T. Changes in neuronal DNA content variation in the human brain during aging. Aging Cell. 2012;11(4):628-33
Results of this indicate that the genomic variation associated with DNA content exceeding the diploid level might compromise viability of these neurons in the aging brain and might thus contribute to susceptibilities for age-related CNS disorders
6. Arendt T, Brückner MK, Mosch B, Lösche A. Selective cell death of hyperploid neurons in Alzheimer's disease. Am J Pathol. 2010;177(1):15-20
This paper shows that neurons with a more-than-diploid content of DNA are increased in preclinical stages of Alzheimer’s disease and are selectively affected by cell death during progression of the disease. Hyperploidy of neurons thus represents a direct molecular signature of cells prone to death in AD and indicates that a failure of neuronal differentiation is a critical pathogenetic event in AD.
7. Enard W, Gehre S, Hammerschmidt K, Hölter SM, Blass T, Somel M, Brückner MK, Schreiweis C, Winter C, Sohr R, Becker L, Wiebe V, Nickel B, Giger T, Müller U, Groszer M, Adler T, Aguilar A, Bolle I, Calzada-Wack J, Dalke C, Ehrhardt N, Favor J, Fuchs H, Gailus-Durner V, Hans W, Hölzlwimmer G, Javaheri A, Kalaydjiev S, Kallnik M, Kling E, Kunder S, Mossbrugger I, Naton B, Racz I, Rathkolb B, Rozman J, Schrewe A, Busch DH, Graw J, Ivandic B, Klingenspor M, Klopstock T, Ollert M, Quintanilla-Martinez L, Schulz H, Wolf E, Wurst W, Zimmer A, Fisher SE, Morgenstern R, Arendt T, de Angelis MH, Fischer J, Schwarz J, Pääbo SA humanized version of Foxp2 affects cortico-basal ganglia circuits in mice. Cell. 2009;137(5):961-71.
This paper shows that the human form of the FOXP2 gene increases synaptic plasticity and dendrite connectivity in the basal ganglia. These results partly explain the enhanced capability of cortico-basal ganglia circuits in the human brain that regulate critical aspects of language, cognition, and motor control.
8. Mosch B, Morawski M, Mittag A, Lenz D, Tarnok A, Arendt T. Aneuploidy and DNA replication in the mormal human brain and Alzheimer´s disease. J Neurosci. 2007; 27:6859-6867
This paper shows an increased single-neurone-DNA-content in AD, associated with re-expression of early mititc markers, indicating a cell-cycle activation in the process of neurodegenerative cell death.
9. Arendt, Th., Stieler, J., Strijkstra, A. M., Hut, R. A., Rüdiger, J., Van der Zee, E. A., Harkany, T., Holzer, M., and Härtig, W. Reversible PHF-like phosphorylation of tau is an adaptive process associated with neuronal plasticity in hibernating animals. J Neurosci. 2003; 18:6972-6981.
highlighted in: Untangling tau. Nature 424 (2003) 898, News and views in brief.
This paper shows that the synaptic plasticity occuring during hibernation is accompanied by reversible changes in the phosphorylation of tau, a protein more commonly associated with neurodegenerative disorder, demonstrating that hypwephosphorylation of tau in the adult mammalian brain is not specific to neurodegnerative processes but rather occurs under conditions of reduced brain metabolism.
10. Arendt, Th., Allen, Y., Sinden, J., Schugens, M. M., Marchbanks, R. M., Lantos, P. L., and Gray, J. A. Cholinergic-rich brain transplants reverse alcohol-induced memory deficits. Nature. 1988;332:448-450.
This paper shows the ability of transplantated cholinergic stem cells to reverse cognitive dysfunction in a rat model of chronic neurodegeneration, providing evidence in support of the cholinergic hypothesis of memory dysfunction.
